A major objective of the studies on isolated acetylcholine receptor is an understanding of the molecular mechanism responsible for its control of ion permeabilities. These studies require that the purified receptor protein be obtained in a state as close to the native functonal state as posssible. Studies of the purified acetylcholine receptor from electric tissue of electric eel and torpedo have rapidly progressed in recent years. However, there are many uncertainties in reports of its basic molecular properties. The discrepancies existing in various reports with respect to the heterogeneity of molecular forms of torpedo acetylcholine receptor have recently been clarified (Chang and Bock, 1977). The heavy form (13 S) is a dimer of the light form (9S) by an intermolecular disulfide bond through 67.000 -dalton subunits. The reduction of this disulfide bond in the 13S form appears to occur to a variable extent during the homogenization of the electric tissue. The analysis suggests that the 13S oligomer is the native form of acetylcholine receptor present in the torpedo membrane. Our preliminary results strongly suggest that a definite relationship between the amount of endogenous phospholipid remaining in the purified receptor and its retention of the original high acetylcholine affinity sites at the equilibrum conditions does exist. Furthermore, in the presence of these endogenous phospholipids, receptor sulfhydryl groups appear to be protected from oxidation. The protection of these sulfhydryl groups presumably prevents the modification of the receptor structure that leads to the permanent alteration of the cholinergic ligant properties. We plan to continue to investigate the nature and the relationship of phospholipid interaction of the acetylcholine receptor and its affinity for acetylcholine and the role of sulfhydryl groups in receptor function and its structure. With improved preparations, various cholinergic ligand and Ca plus ion binding properties will be investigated. The syntheses of new affinity fluorescent probes for the acetylcholine receptor are proposed. Cholinergic ligant induced conformational changes in labeled acetylcholine receptor will be studied.